Project I: Borage Oil and Ginkbo biloba (EGb 761) in Asthma, ME Gershwin, PI overall; V Ziboh, PI of Oil, Co-Invest; SS Teuber, PI of Ginkbo biloba; M Harkey, JB German & c Cross, Co-Invest; J Utts, M Watnik, AL Klassen, Statistics and Database Management; H Watanabe, Consultant The concept of asthma as a condition in which acute and chronic inflammatory changes in airways play a fundamental role is well established. The role of leukotrienes as a crucial element of these inflammatory processes is supported by abundant laboratory and clinical evidence. There is a potential for herbal medicinal approaches to ameliorate leukotriene-mediated inflammation in asthma based on data from the literature and our laboratory. Studies suggest that dietary gamma-linolenic (GLA), found in borage and evening primrose oil, is unique among the (n=6) polyunsaturated fatty acid family members (linolenic acid, GLA and arachidonic acid) in its potential to attenuate inflammatory processes. For instance, there are randomized, placebo- controlled trials (RCT) demonstrating efficacy of dietary GLA in patients with rheumatoid arthritis and active synovitis. Ginkbo biloba, a flavonoid-rich extract of leaves of the Ginkbo biloba tree, has been studied in one RCT with asthma patients and is recommended by CAM practitioners as a treatment of allergic inflammation and asthma. Ginko biloba may have inhibitory effects on release of inflammatory mediators. Although improvements has been made in management of patients with asthma, may interventions are associated with adverse effects. Because of the possibility of minimal or negligible adverse effects reported with borage oil, and the widespread use of Ginkgo biloba supplements without known adverse effects, we will assess clinical efficacies and/or adverse effects of dietary borage oil containing GLA and Ginkbo biloba in patients with asthma in a 17 month RCT. We also propose to delineate whether or not the clinical course of treatment correlates with suppression of leukotriene B4 (LTB4), LTC4 and LTD4, generated by activated polymorphonuclear cells (PMNs). Additionally, in the Ginkgo biloba arm of study, the vitro/ex vivo inhibition of histamine release will be assayed, since one of its major constituents, quercetin, is known to be structurally related to cromolyn sodium and has been shown in in vitro studies to exhibit similar activities. Furthermore. Anti-inflammatory activities of Ginkbo biloba will be compared to those of some of its individual constituents in a series of in vitro experiments. It is hoped that findings from these studies will evolve relatively non-toxic therapeutic alternatives for attenuating bronchial hyperresponsiveness and inflammation in patients with asthma.